COURSE INFORMATION The following text is a summary of a two-hour lecture sequence presented in the course, Advanced Medicinal Chemistry I. This course is required for all MS and PhD students in Duquesne University’s Medicinal Chemistry Graduate Program. It is also available as an elective for undergraduate students in their last semester of didactic work. The course emphasizes the basic chemica...

Here we compare the structural and evolutionary attributes of Thermus thermophilus and Escherichia coli small ribosomal subunits (SSU). Our results indicate that with few exceptions, thermophilic 16S ribosomal RNA (16S rRNA) is densely packed compared to that of mesophilic at most of the analogous spatial regions. In addition, we have located species-specific cavity clusters (SSCCs) in both spe...

Protein crystallography data collection at synchrotrons is routinely carried out at cryogenic temperatures to mitigate radiation damage. Although damage still takes place at 100 K and below, the immobilization of free radicals increases the lifetime of the crystals by approximately 100-fold. Recent studies have shown that flash-cooling decreases the heterogeneity of the conformational ensemble ...

Abstract The Protein Ensemble Database (PED; https://proteinensemble.org/ ) is the major repository of conformational ensembles intrinsically disordered proteins (IDPs). Conformational IDPs are primarily provided by their authors or occasionally collected from literature, and subsequently deposited in PED along with corresponding structured, manually curated metadata. modeling usually relies on...

Histone tails are highly flexible N- or C-terminal protrusions of histone proteins which facilitate the compaction of DNA into dense superstructures known as chromatin. On a molecular scale histone tails are polyelectrolytes with high degree of conformational disorder which allows them to function as biomolecular "switches", regulating various genetic processes. Unfortunately, their intrinsical...

The periplasmic sensor domains GSU0582 and GSU0935 are part of methyl accepting chemotaxis proteins in the bacterium Geobacter sulfurreducens. Both contain one c-type heme group and their crystal structures revealed that these domains form swapped dimers with a PAS fold formed from the two protein chains. The swapped dimerization of these sensors is related to the mechanism of signal transducti...

Merozoite surface protein 2 (MSP2) of Plasmodium falciparum is an abundant, intrinsically disordered protein that is GPI-anchored to the surface of the invasive blood stage of the malaria parasite. Recombinant MSP2 has been trialled as a component of a malaria vaccine, and is one of several disordered proteins that are candidates for inclusion in vaccines for malaria and other diseases. Nonethe...